Among the tubular dysfunctions of the diabetic nephron are a concentrating defect and a distal acidification defect. In isolated perfused tubule experiments, stilbene disulfonate-sensitive anion exchange has been implicated both in collecting duct (CD) acidification mechanisms, and in medullary thick ascending limb (MTAL) cell volume regulation in response to normal medullary interstitial (NaCl) changes. The transport proteins responsible for these anion movements have not been identified. However, by the criteria of inhibitor sensitivity, kinetic mechanism, and more recently, immunoreactivity and nuclei acid hybridization some of these proteins are structurally related to the erythroid C1- /HCO3-exchanger, band 3. DNA sequence has confirmed this hypothesis for the first such protein. This proposal will exploit a large set of newly isolated cDNA and genomic clones to characterize additional members of this growing, band 3-related gene family. By characterizing the clones, sequencing the full-length cDNAs, preparing antisera which recognize the gene products and which if possible, discriminate among them, a panel of hybridization and immunological reagents will be assembled. This panel of reagents will allow subsequent high-resolution study of the structure, function and regulation of band 3-related proteins in kidney and in other tissues. The results of these studies will provide a new context in which to understand and perhaps influence, the course of tubular dysfunction in the diabetic kidney.